Scientists have known for years that a successful cure must get rid of these hidden pockets of HIV. The question has been how.
Finally, some answers are turning up. In fact, researchers have found two compounds that might hold the key to getting rid of the viral reservoirs. Bryologs and didehydro-cortistatin A (dCA)
Several years ago researchers found a chemical called a bryostatin in a bryozoan – a tiny sea creature that grows in colonies like a big bunch of moss. This bryostatin showed promise for treating HIV and several other diseases. It did something new in HIV research – it activated the HIV reservoirs so the immune system and HAART could find and get rid of them.
Unfortunately, bryostatin is very hard to get. It takes tons of bryozoans to extract a few grams of bryostatin. Clinical trials of bryostatin stopped because there wasn’t enough of it.
Recently researchers at Stanford, led by Paul Wendel, have found a way to make synthetic versions of bryostatin, called bryologs. The bryologs are relatively easy to manufacture and in early testing appear to be more effective at flushing HIV reservoirs than the original bryostatins.
Testing for bryologs is still in early stages, and it will probably be a few years before they are ready for clinical trials. Bryologs are one possible answer to the challenge of viral reservoirs.
didehydro-cortistatin A (dCA)
Another possible way to clear out viral reservoirs comes for a different marine animal. A sponge known as Corticium simplex has provided a compound which can eliminate HIV from infected cells. This compound has been synthesized at the Scripps Research Institute and the synthesized version is called didehydro-cortistatin A or dcA for short.
dcA is a big deal because current ARVs don’t clear out infected cells, they only stop new infections from happening. dcA works in infected cells by interfering with the way the virus interacts with the cells DNA. A virus reproduces by adding it’s DNA to a cell, and tricking the cell into making more viruses. By interfering with the DNA interaction, dcA can prevent an infected cell from making new viruses.
The threat of viral reservoirs has always been in their ability to churn out new viruses. Traditional ARVs can clear out all the HIV in the bloodstream and prevent new cells from being infected, but as long as the viral reservoirs are able to start creating new viruses at a moments notice, it will never be safe for people with HIV/AIDS to stop taking ARVs. If dcA works the way researchers think it will, then once the infection is under control, it may be possible for a person to stop taking ARVs, because the viral reservoirs won’t be able to produce any new viruses to re-start the infection.
In the lab, that seems to be what is happening. Infected cell cultures that are treated with traditional ARVs will start producing more HIV as soon as the ARV is stopped. But tests of dcA at Scripps have shown that when an infected cell culture is treated with dcA, and the treatment is stopped, the infection does not come back. If scientists can make dcA into a medication, then it will bring us a huge step closer to a functional cure for HIV.
dcA is called an anti-Tat inhibitor because of the way it works. (TAT is a biology term for one step of the virus messing with the host cells DNA). dcA is not the first anti-TAT inhibitor researchers have found, but other anti-Tat inhibitors failed in clinical trials. Scripps researchers believe that dcA has a good chance of passing clinical trials. Its structure is already drug-like, which means it should be absorbed into the body easily. It works in small amounts, which means it is less likely to have dangerous side effects or toxicities. And it is more successful in lab tests than any prior anti-Tat inhibitor.
Neither bryologs nor dcA are ready to be used as medication. They have a number of steps to go through before they are even ready to start clinical trials. But the early steps look hopeful. If either of them passes clinical trials to become a new medication for HIV it will be a major change in the fight against HIV. If both pass clinical trials, we may see the approach to treating HIV take on a whole new direction. Most importantly, we know there are things out there which can combat the viral reservoirs. If these compounds can’t be turned into effective medication, we can be sure of finding or building others that may.